Plasma Human Immunodeficiency Virus 1 Soluble Glycoprotein 120 Association With Correlates of Immune Dysfunction and Inflammation in Antiretroviral Therapy-Treated Individuals With Undetectable Viremia

被引：10

作者：

Benlarbi, Mehdi ^{[1
,2
]}

Richard, Jonathan ^{[1
,2
]}

Bourassa, Catherine ^{[1
]}

Tolbert, William D. ^{[3
]}

Chartrand-Lefebvre, Carl ^{[4
]}

Gendron-Lepage, Gabrielle ^{[1
]}

Sylla, Mohamed ^{[1
]}

El-Far, Mohamed ^{[1
]}

Messier-Peet, Marc ^{[1
]}

Guertin, Camille ^{[1
,2
]}

Turcotte, Isabelle ^{[1
,2
]}

Fromentin, Remi ^{[1
,2
]}

Verly, Myriam Maude ^{[1
]}

Prevost, Jeremie ^{[1
,2
]}

Clark, Andrew ^{[5
]}

Mothes, Walther ^{[6
]}

Kaufmann, Daniel E. ^{[1
,7
,8
]}

Maldarelli, Frank ^{[9
]}

Chomont, Nicolas ^{[1
,2
]}

Begin, Philippe ^{[10
,11
]}

Tremblay, Cecile ^{[1
,2
]}

Baril, Jean-Guy ^{[12
,13
]}

Trottier, Benoit ^{[12
,13
]}

Trottier, Sylvie ^{[14
]}

Duerr, Ralf ^{[15
,16
,17
]}

Pazgier, Marzena

Durand, Madeleine ^{[1
,11
,19
]}

Finzi, Andres ^{[1
,2
,18
]}

机构：

[1] Ctr Rech CHUM, Montreal, PQ, Canada

[2] Univ Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ, Canada

[3] Uniformed Serv Univ Hlth Sci, Dept Med, Infect Dis Div, Bethesda, MD USA

[4] Univ Montreal, Dept Radiol Radiat Oncol & Nucl Med, Montreal, PQ, Canada

[5] ViiV Healthcare, Global Med Affairs, Brentford, Middx, England

[6] Yale Univ, Sch Med, Dept Microbial Pathogenesis, New Haven, CT USA

[7] Lausanne Univ Hosp, Dept Med, Div Infect Dis, Lausanne, Switzerland

[8] Univ Lausanne, Lausanne, Switzerland

[9] NCI, HIV Dynam & Replicat Program, NIH, Bethesda, MD USA

[10] Dept Pediat, Sect Allergy Immunol & Rheumatol, CHU Sainte Justine, Montreal, PQ, Canada

[11] Ctr Hospitalier Univ Montreal, Fac Med, Dept Med, Montreal, PQ, Canada

[12] Clin Med Urbaine Quartier Latin, Montreal, PQ, Canada

[13] Univ Montreal, Dept Med Familiale, Montreal, PQ, Canada

[14] Univ Laval, Ctr Rech Ctr hospitalier Univ Quebec, Dept Microbiol infectiol & immunol, Quebec City, PQ, Canada

[15] NYU, Vaccine Ctr, Grossman Sch Med, New York, NY USA

[16] NYU, Dept Med, Grossman Sch Med, New York, NY USA

[17] NYU, Dept Microbiol, Grossman Sch Med, New York, NY USA

[18] Ctr Rech CHUM CRCHUM, 900 Rue St Denis,Tour Viger R09-420, Montreal, PQ H2X 0A9, Canada

[19] Ctr Rech CHUM CRCHUM, 850 Rue St Denis,Tour St Antoine SO2-824, Montreal, PQ H2X 0A9, Canada

来源：

JOURNAL OF INFECTIOUS DISEASES | 2024年 / 229卷 / 03期

基金：

美国国家卫生研究院; 加拿大健康研究院; 加拿大创新基金会;

关键词：

HIV-1; soluble gp120; anti-cluster A antibodies; chronic inflammation; cardiovascular diseases; GP120 INNER DOMAIN; CYTOTOXICITY-MEDIATING ANTIBODIES; DEFECTIVE HIV-1 PROVIRUSES; ENVELOPE GLYCOPROTEIN; COMPUTED-TOMOGRAPHY; EPITOPES; IDENTIFICATION; FOSTEMSAVIR; INFECTION; EFFICACY;

D O I：

10.1093/infdis/jiad503

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background Chronic inflammation persists in some people living with human immunodeficiency virus (HIV) during antiretroviral therapy and is associated with premature aging. The glycoprotein 120 (gp120) subunit of HIV-1 envelope sheds and can be detected in plasma, showing immunomodulatory properties even in the absence of detectable viremia. We evaluated whether plasma soluble gp120 (sgp120) and a family of gp120-specific anti-cluster A antibodies, linked to CD4 depletion in vitro, contribute to chronic inflammation, immune dysfunction, and subclinical cardiovascular disease in participants of the Canadian HIV and Aging Cohort Study with undetectable viremia.Methods Cross-sectional assessment of sgp120 and anti-cluster A antibodies was performed in 386 individuals from the cohort. Their association with proinflammatory cytokines and subclinical coronary artery disease was assessed using linear regression models.Results High levels of sgp120 and anti-cluster A antibodies were inversely correlated with CD4+ T cell count and CD4/CD8 ratio. The presence of sgp120 was associated with increased levels of interleukin 6. In participants with detectable atherosclerotic plaque and detectable sgp120, anti-cluster A antibodies and their combination with sgp120 levels correlated positively with the total volume of atherosclerotic plaques.Conclusions This study showed that sgp120 may act as a pan toxin causing immune dysfunction and sustained inflammation in a subset of people living with HIV, contributing to the development of premature comorbid conditions. Soluble glycoprotein 120 (sgp120) is detected in the plasma of people living with HIV-1 with undetectable viremia. The presence of sgp120 and anti-cluster A antibodies is associated with correlates of immune dysfunction, chronic inflammation, and subclinical cardiovascular disease.

引用

页码：763 / 774

页数：12

共 45 条

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